【摘要】 目的探讨伤害性杏仁核（CeLC）中代谢型谷氨酸受体5（mGluR5）对阿片诱导痛觉过敏（OIH）大鼠杏仁核神经通路兴奋性突触传递的影响。方法实验一:取SD雄性大鼠18只,随机分为对照组（C组）、痛觉过敏+DMSO组（OIH+DMSO组）和痛觉过敏+mGluR5选择性拮抗剂组（OIH+MTEP组）,每组6只。三组大鼠均接受右侧CeLC置管,恢复1周后OIH+DMSO组和OIH+MTEP组经皮下注射芬太尼造OIH模型,芬太尼剂量为60μg/kg,4次,间隔时间15 min,C组皮下注射等容量生理盐水。6.5 h后OIH+DMSO组大鼠CeLC区注射10%二甲基亚砜（DMSO）0.5μl;C组和OIH+MTEP组大鼠CeLC区注射MTEP 15μg。观察造模前（T₀）、造模后（T₁）和给药后（T₂）大鼠机械缩足阈值（WMT）和热缩足反射潜伏期（TWL）。实验二:另取10只大鼠随机分为正常组（N组）和痛觉过敏组（OIH组）,OIH组注射芬太尼造OIH模型,N组注射等容量生理盐水。使用双电极膜片钳技术分别记录使用MTEP前后两组大鼠基底外侧杏仁核（BLA）-CeLC神经通路刺激诱发的兴奋性突触后电流（eEPSCs）的幅值。结果实验一:与T₀时比较,T₁时OIH+DMSO组与OIH+MTEP组大鼠WMT明显降低、TWL明显缩短（P<0.05）;与T₁比较,T₂时OIH+MTEP组大鼠WMT明显升高、TWL明显延长（P<0.05）;T₂时OIH+MTEP组WMT明显高于OIH+DMSO组,TWL明显长于OIH+DMSO组（P<0.05）,T₂时OIH+MTEP组和C组WMT及TWL差异无统计学意义。实验二:与OIH组使用MTEP前比较,OIH组使用MTEP后eEPSCs幅值明显降低。N组使用MTEP前和N组使用MTEP后eEPSCs幅值差异无统计学意义。OIH组使用MTEP前eEPSCs幅值明显高于N组使用MTEP前（P<0.05）。结论激活CeLC中mGluR5可通过增强BLA-CeLC神经通路的兴奋性突触传递来参与调控芬太尼诱导的痛觉过敏。更多还原

【Abstract】 Objective To investigate the effect of metabolic glutamate receptor 5（mGluR5） in nociceptive amygdala（the laterocapcular division of central amygdala, CeLC） on excitatory synaptic transmission in amygdaloid neural pathway in rats with opioid-induced hyperalgesia（OIH）. Methods Experiment 1∶18 male SD rats were randomly divided into the control group（group C）, the hyperalgesia + DMSO group（group OIH+DMSO） and the hyperalgesia + mGluR5 selective antagonist group（group OIH+MTEP）, with 6 rats in each group. All rats in the three groups received CeLC catheterization on the right side. After one week of recovery, group OIH+DMSO and group OIH+MTEP received subcutaneous injection of fentanyl to establish OIH model. The dose of fentanyl was 60 μg/kg, 4 times, with an interval of 15 min. Group C was subcutaneously injected with saline of equal volume.After 6.5 h, rats in the group OIH+DMSO were injected with 10% DMSO 0.5 μl in the CeLC. Rats in the group C and group OIH+MTEP were injected with MTEP 15 μg in the CeLC. The changes of mechanical withdrawal threshold（WMT） and thermal withdrawal latency（TWL） were tested pre-OIH（T₀）, post-OIH（T₁）, and post-drug（T₂）. Experiment 2: another 10 rats were randomly divided into 2 groups: the normal group（group N） and the hyperalgesia group（group OIH）. Group OIH was injected with fentanyl to make OIH model, and group N was injected with normal saline of equal volume. The amplitude of evoked excitatory postsynaptic currents（eEPSCs） of the basolateral amygdala（BLA）-CeLC neural pathway before and after administration of MTEP was recorded by using double electrode patch clamp technique. Results Experiment 1: Compared with T₀,WMT and TWL of rats in group OIH+DMSO and group OIH+MTEP were significantly decreased and shortened at T₁. Compared with T₁, WMT was significantly increased and TWL was significantly prolonged in rats of group OIH+MTEP at T₂. Compared with group OIH + DMSO, WMT was significantly increased and TWL was significantly prolonged in group OIH+MTEP at T₂（P < 0.05）. There was no significant difference in WMT and TWL between group OIH + MTEP and group C at T₂. Experiment 2: Compared with the group OIH pre-MTEP, the amplitude of eEPSCs in the group OIH was significantly decreased post-MTEP. There was no significant difference in eEPSCs amplitude between group N pre-MTEP and group N post-MTEP. The amplitude of eEPSCs in group OIH pre-MTEP was significantly higher than group N pre-MTEP（P < 0.05）. Conclusion Activation of mGluR5 in the CeLC may be involved in the regulation of fentanyl-induced hyperalgesia by enhancing excitatory synaptic transmission in the BLA-CeLC neural pathway.更多还原